TY - JOUR A1 - Pétry, Nicolas A1 - Benakki, Hafid A1 - Clot, Eric A1 - Retailleau, Pascal A1 - Guenoun, Farhate A1 - Asserar, Fatima A1 - Sekkat, Chakib A1 - Métro, Thomas-Xavier A1 - Martinez, Jean A1 - Lamaty, Frédéric T1 - A mechanochemical approach to access the proline–proline diketopiperazine framework JF - Beilstein Journal of Organic Chemistry PY - 2017/// VL - 13 SP - 2169 EP - 2178 SN - 1860-5397 DO - 10.3762/bjoc.13.217 PB - Beilstein-Institut JA - Beilstein J. Org. Chem. UR - https://doi.org/10.3762/bjoc.13.217 KW - ball mill KW - DFT calculations KW - diketopiperazine KW - mechanochemistry KW - pyrrolidine N2 - Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution. Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline–proline dipeptides under solvent-free conditions. A deprotection–cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be explained by DFT calculations. Using this method, an enantiopure disubstituted Pro–Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill. ER -